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Updated: Jun 23, 2025

High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication
10:16

High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication

Published on: October 30, 2021

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Zika virus non-coding RNAs antagonize antiviral responses by PKR-mediated translational arrest

Horacio M Pallarés1, María Mora González López Ledesma1, Santiago Oviedo-Rouco1

  • 1Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires IIBBA-CONICET, Ciudad Autónoma de Buenos Aires, Argentina.

Nucleic Acids Research
|June 25, 2024
PubMed

Insights

Zika virus (ZIKV) uses small viral RNAs (sfRNAs) to block antiviral gene translation. These sfRNAs hijack the PKR pathway, turning an antiviral defense into a factor that boosts viral production.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Zika virus (ZIKV) is a mosquito-borne flavivirus causing significant human outbreaks.
  • ZIKV infection produces small viral RNAs (sfRNAs) essential for viral pathogenesis and immune evasion.
  • The precise mechanisms by which sfRNAs operate remain incompletely understood.

Purpose of the Study:

  • To elucidate the functional mechanisms of ZIKV sfRNAs in host-pathogen interactions.
  • To investigate how sfRNAs influence the translation of antiviral genes.
  • To understand the role of PKR activation in ZIKV replication and pathogenesis.

Main Methods:

  • Utilized recombinant ZIKV strains for infection models.
  • Employed ribosome profiling in infected human cells to assess translation efficiency.
  • Analyzed the impact of sfRNAs and PKR activation on viral and host gene expression.

Main Results:

  • ZIKV sfRNAs were found to inhibit the translation of antiviral genes.
  • Specific RNA structures within sfRNAs trigger Protein Kinase R (PKR) activation.
  • PKR activation, induced by ZIKV sfRNAs, paradoxically enhanced viral particle production.
  • Translation of type I interferon and interferon-stimulated genes was significantly reduced.

Conclusions:

  • ZIKV employs sfRNAs as a novel mechanism to adapt and enhance its fitness.
  • The virus effectively repurposes the host's antiviral factor, PKR, into a proviral one.
  • This study reveals a sophisticated viral strategy for immune evasion and replication.

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